Targeted chemotherapy of visceral leishmaniasis by lactoferrin-appended amphotericin B-loaded nanoreservoir: in vitro and in vivo studies

Abstract

Aim: Exploitation of lactoferrin-appended amphotericin B bearing nanoreservoir (LcfPGNP-AmB) for targeted eradication of Leishmania donovani. Materials and Methods: LcfPGNP-AmB was architechtured through ionic adsorption of lactoferrin over core poly (d,l-lactide-co-glycolide) nanoparticles and characterized. Anti-Leishmania activity in visceral leishmaniasis models, immunomodulatory potential, biodistribution and toxicity profile were also assessed. Results: LcfPGNP-AmB (size, 196.0 ± 5.28 nm; zeta-potential, +21.7 ± 1.52 mV; encapsulation efficiency, ∼89%) showed reduced toxicity, increased protective proinflammatory mediators expression and down-regulation of disease-promoting cytokines. Biodistribution study illustrated preferential accumulation of LcfPGNP-AmB in liver and spleen. LcfPGNP-AmB showed augmented antileishmanial activity by significantly reducing (∼88%) splenic parasite burden of infected hamsters, compared with commercial-formulations. Conclusion: Superior efficacy, desired stability and reliable safety of cost-effective LcfPGNP-AmB, suggest its potential for leishmaniasis therapeutics.